Short-term rapid ventricular pacing prolongs ventricular refractoriness in patients.

BACKGROUND: Traditional concepts suggest that ventricular refractoriness should gradually shorten during rapid pacing and gradually return to baseline after termination of pacing. Animal data, however, have shown that under certain circumstances sustained rapid ventricular rates can prolong refractoriness and action potential duration and, thereby, promote ventricular arrhythmias. METHODS AND RESULTS: In humans we evaluated the effect of rapid pacing (cycle length 400 msec for 30 min from either the right ventricular apex [RVA, 13 patients] or high right atrium [HRA, 11 patients]) on the ventricular effective refractory period (VERP) as measured from the RVA, using the extrastimulus method (drive train 500 msec). A control group of seven patients had serial measurements of VERPs in the absence of pacing. For a given patient, all VERPs were measured at constant stimulus output (twice diastolic threshold) from the same ventricular site and at the same drive train cycle length. VERPs obtained immediately following rapid pacing did not differ from those at baseline (P = 0.46); however, VERPs obtained 15 minutes post pacing were prolonged compared with baseline VERPs (231 +/- 20 msec vs 246 +/- 23 msec, P < 0.0026). Pacing site has no impact on VERP prolongation. There was no effect of time on VERP in the absence of pacing. CONCLUSION: In contrast to traditional concepts of refractoriness, after the termination of sustained rapid ventricular rates, VERP prolonged. This phenomenon could help explain the observation of torsades de pointes in some patients after atrioventricular junction ablation or the administration of a Class IA antiarrhythmic agent to convert atrial fibrillation with rapid ventricular response to sinus rhythm.

Histamine and protein transport in canine muscle.

The effect of intraarterial histamine infusion on transcapillary protein transport was determined in the constant flow pump-perfused isolated gracilis muscle of the dog. Muscle vascular resistance (MVR), the rate of net transcapillary protein transport (Js), net transcapillary fluid transport (Jv), changes in protein-free transcapillary fluid movement (delta Jo) and rubidium extraction (ERb) were calculated following four experimental manipulations. First, as a control, venous pressure was elevated by 20 mmHg; next, histamine was infused intraarterially; then venous pressure was elevated by 20 mmHg during histamine infusion; and finally, the recovery of the tissue from histamine infusion was determined. Although elevation of venous pressure produced no change in MVR, it significantly increased Js, Jv and delta Jo. Histamine infusion caused a significant decline in MVR, and increases in Js and in Jv. delta Jo did not change significantly. When venous pressure elevation was superimposed upon histamine infusion, MVR did not change; Js, Jv, and delta Jo increased but only by increments similar to venous pressure elevation alone. None of the manipulations altered Rb extraction. At the constant flow used in this study, histamine does not appear to increase either capillary hydrostatic pressure or capillary surface area, so that the small intestine in Js was probably due to a slight increase in capillary permeability.

Polyarteritis nodosa: chronic renal failure with spontaneous recovery.

A 57-year-old male developed acute oliguric renal failure due to polyarteritis nodosa (PAN). He went on rapidly to chronic renal failure. After nine months of home hemodialysis, he recovered renal function with creatinine clearance of 30 ml/min. This patient was not treated with drugs of any type for his illness. He represents a spontaneous remission from severe renal PAN and underscores the need for further evaluation of the current recommended drug therapy for this disease.

Normokalemic nonazotemic adrenal insufficiency.

Two patients had adrenal insufficiency with severe hyponatremia and profound central nervous system symptoms. In both adrenal insufficiency was diagnosed clinically. Neither patient had either hyperkalemia or azotemia.

Renal tubular acidosis in pregnancy.

Two pre-eclamptic females were seen in consultation by the Renal Service. Both had Renal Tubular Acidosis (RTA). One case resulted from the possible exacerbation of Lupus Erythematosus. The other patient's RTA seemed to be related to ingestion of Dyazide for pre-eclampsia. Delivery of the child in the first case and discontinuance of Dyazide in the second resulted in the abrupt disappearance of RTA.

The effect of hemodialysis on oxygen transport in chronic uremics.

Previous studies from our laboratory suggested a decrease in tissue oxygen delivered during hemodialysis of chronic uremic patients due to an increase in hemoglobin-oxygen affinity, i.e. decrease in P50. This current study was designed to determine whether the changes in cardiac index and/or tissue oxygen extraction could compensate for increases in hemoglobin-oxygen affinity previously observed, so that total tissue delivery was unchanged during hemodialysis. This study demonstrated in patients during a 6-hour hemodialysis that: 1) no change occurs in hemoglobin-oxygen affinity expressed as P50, with unchanging plasma inorganic phosphate and red blood cell pH; 2) increased extraction of oxygen from tissue, measured via (A-V) O2 difference compensates for decreased oxygen delivery due to decreased cardiac output, and although there was no demonstrable change in hemoglobin-oxygen affinity, it would appear that increased tissue extraction of oxygen via other mechanisms should be easily able to compensate for previously reported changes in P50.

The importance of microscopic examination of the urinary sediment.

Urinalysis may provide evidence of significant renal disease in asymptomatic patients. The microscopic urinalysis is vital to making diagnoses in many asymptomatic cases, including urinary tract infection, urinary tract tumors, occult glomerulonephritis, and interstitial nephritis. Three-hundred-fifty-three consecutive urinalyses were performed in our Urinalysis Laboratory to discern the incidence of significant urinary findings not disclosed by macroscopic examination. One-hundred-seventy-two urines had negative macroscopic exams, but 52 of these had positive microscopic findings, an incidence of 30% (52/172). Furthermore, 15% (52/353) of all urines studied revealed significant urinary findings microscopically. An adequate examination of the urine must include a microscopic as well as a macroscopic examination.

Mass-balance approach for estimating transcapillary fluid and protein movement.

This study assesses the applicability of a procedure based on mass conservation to estimate transcapillary protein transport (PT) in patients. In a tissue that exhibits net transcapillary protein transport, total transcapillary fluid movement (FMT) is defined according to the law of mass conservation as: FMT = FA (CV - CA)/CV + PT/CV where FA is arterial plasma flow and CV and CA are respectively venous and arterial protein concentration. The first term above (FMO) was estimated from changes in venous plasma oncotic pressure. The second term was estimated both from the rate of tissue accumulation of 125I-albumin and from the mass-balance relationship as (FMT - FMO). FMT was determined in a jejunal segment as the sum of the changes in tissue weight, fluid secretion, and lymph flow. Increasing venous pressure by 10 and 20 mmHg produced changes in FMT and PT which, as estimated by the two methods, were not significantly different. Thus PT can be estimated from the mass-balance relationship without employing either radioactive labels or noxious tissue manipulation; such an approach should be suitable for clinical application.

Urinalysis and clinical renal disease.

Urinalysis is a simple, efficient, and accurate guide in the diagnosis of renal disease. By determining a patient's history and obtaining a physical examination, the physician is very often able to diagnose a patient's renal lesion. Heavy proteinuria and a microscopic sediment containing red cells and red cell casts strongly suggest acute glomerulonephritis. The causes of this nephropathy are legion. On the other hand, mild proteinuria and a lack of microscopic findings suggest nephrosclerosis, interstitial nephritis, or acute tubular necrosis in the proper clinical setting. When glomerular disease produces nephrotic syndrome, the various types of glomerular disease can be diagnosed accurately without biopsy in a high percentage of cases.

Effect of intravenous mannitol on renal hemodynamics and renal lymph recovery during acute ureteral obstruction.

The object of this study was to determine the effect of mannitol upon lymph flow during acute unilateral renal obstruction in the dog--whether it would sustain, increase, or have an adverse effect upon renal hilar lymph flow. Two groups of dogs were used so that the efficacy of bolus injection could be compared with continuous infusion of mannitol. After ureteral obstruction renal hilar lymph flow increased significantly. Renal artery pressure, venous pressure, blood flow, and lymph flow were sustained by both bolus and continuous infusion. These results show that intravenous mannitol given during acute ureteral obstruction will sustain an increase in renal hilar lymph flow.

Hypoxanthine-arabinoside pharmacokinetics after adenine arabinoside administration to a patient with renal failure.

Hypoxanthine arabinoside pharmacokinetics were measured during an adenine arabinoside continuous intravenous infusion and during hemodialysis in a patient with renal failure. Therapeutic guidelines for adenine arabinoside in renal failure are provided based on an elimination half-life of 4.7 h and a plasma clearance of 87.9 ml/min for the hypoxanthine metabolite.

A beneficial effect of splenectomy in sickle cell anemia and chronic renal failure.

A 25-year-old black male with known sickle cell disease developed progressive chronic renal failure. Eight months after the initiation of chronic hemodialysis, he developed a rapidly-increasing transfusion requirement. The requirement was one unit of blood per week in order to maintain a hematocrit of 16%. His spleen was found, at that time, to be enlarged both on physical examination and radioisotopic scan. A radiochromium study disclosed a red blood cell half-life of 17 days. No evidence of splenic sequestration could be demonstrated isotopically. Splenectomy produced a marked decrease in the patient's transfusion need. Presently, this patient needs one unit of blood every 10 to 12 weeks to maintain a hematocrit of 18%.

Diuretics, hepatic and thoracic duct lymph flows in the dog.

1. Simultaneous thoracic duct and hepatic lymph flows were measured in 29 mongrel dogs before and after the intravenous administration of mannitol, ethacrynic acid, frusemide and chlorothiazide in separate experiments. 2. Thoracic duct lymph flow increased significantly after each diuretic agent was administered. 3. Hepatic lymph flow increased only after ethacrynic acid and mannitol administration. Frusemide and chlorothiazide did not alter hepatic lymph flow. 4. These data show that increases in thoracic duct lymph flow after ethacrynic acid and mannitol arise partly from the liver, as well as from other organs.

Hypercalcaemia due to hyperparathyroidism in a patient with chronic renal failure and renal carcinoma.

A 65-year-old woman with a history of a left heminephrectomy for renal carcinoma developed hypercalcaemia 11 years after the operation. The same kidney was found to contain a recurrent renal carcinoma. After the radical nephrectomy of the left kidney, hypercalcaemia remitted but reappeared 11 months later. The right kidney was small but functioned at a level of creatinine clearance of 10--15 ml/min. Metastatic work-up was negative, and secondary causes of hypercalcaemia were excluded. A neck exploration revealed a parathyroid adenoma. With parathyroid resection the serum calcium declined to normal, and the risk of hypercalcaemic nephropathy in the remaining kidney was precluded.

Minoxidil treatment of malignant hypertension. Recovery of renal function.

We treated eight severely hypertensive, long-term hemodialysis patients who failed to respond to ultrafiltration or conventional medication with minoxidil rather than with bilateral nephrectomy. Control of blood pressure and relief of symptoms was achieved in all eight. In addition, three of the patients, who were all severely oliguric, recovered sufficient renal function to allow the discontinuation of dialysis. Two are presently doing well, while one died of causes unrelated to uremia or minoxidil therapy. We presently reserve bilateral nephrectomy for those hypertensive dialysis patients who are awaiting transplantation.